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Antimicrobial Agents and Chemotherapy, July 2009, p. 2841-2845, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01408-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Noncanonical Vancomycin Resistance Cluster from Desulfitobacterium hafniense Y51{triangledown}

Lindsay Kalan,1 Sara Ebert,2 Tom Kelly,3 and Gerard D. Wright1*

Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada,1 Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada,2 Department of Microbiology, St. Josephs' Health Care, Hamilton, Ontario, Canada3

Received 20 October 2008/ Returned for modification 16 December 2008/ Accepted 17 April 2009

The glycopeptide vancomycin is a drug of last resort for infection with gram-positive organisms, and three genes are vital to resistance: vanH, vanA, and vanX. These genes are found in a vanHAX cluster, which is conserved across pathogenic bacteria, glycopeptide antibiotic producers, and other environmental bacteria. The genome sequence of the anaerobic, gram-positive, dehalogenating bacterium Desulfitobacterium hafniense Y51 revealed a predicted vanA homolog; however, it exists in a vanAWK-murFX cluster, unlike those of other vancomycin-resistant organisms. Using purified recombinant VanA from D. hafniense Y51, we determined its substrate specificity and found it to have a 42-fold preference for D-lactate over D-alanine, confirming its activity as a D-Ala-D-Lac ligase and its annotation as VanA. Furthermore, we showed that D. hafniense Y51 is highly resistant to vancomycin, with a MIC for growth of 64 µg/ml. Finally, vanADh is expressed during growth in vancomycin, as demonstrated by reverse transcription-PCR. This finding represents a new glycopeptide antibiotic resistance gene cluster and expands the genetic diversity of resistance to this important class of antibiotic.

* Corresponding author. Mailing address: Institute for Infectious Disease Research, McMaster University, 1200 Main St. W, Hamilton, Canada L8N 3Z5. Phone: (905) 525-9140. Fax: (905) 522-9033. E-mail: wrightge{at}mcmaster.ca

{triangledown} Published ahead of print on 4 May 2009.

Antimicrobial Agents and Chemotherapy, July 2009, p. 2841-2845, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01408-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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